Higher BDNF Levels Research Articles

Temporal distribution of mRNA expression levels of various genes in the developing human inferior colliculus

The inferior colliculus (IC) is a major binaural integration center in the auditory pathway. Interestingly, studies on the prenatal development of the human IC are lacking. During development of the nervous system a large repertoire of proteins is involved in transforming simple neuroblast cells into functional elements of the adult neural circuits. The present study reports on the mRNA levels produced by 12 genes involved in pre- [12–29 weeks of gestation (WG)], postnatal [40 postnatal days (PND) as well as 2 and 5 postnatal months (PNM)] developing human IC. The mRNA expression levels of nestin, vimentin, GFAP and DCX during 12–24 WG indicate the stages of neurogenesis, migration and differentiation of the human fetal IC. A decrease in the GAP-43 mRNA levels along with an increase in synaptophysin and PSD-95 mRNA levels during late gestational ages (24–29 WG) suggests the formation of primitive contacts by neurons with their targets and the onset of synapse formation. Expression levels of EGAD mRNA were transient with an increase in the early gestational ages, whereas that of GAD-67 mRNA increased in late gestational ages, indicating the changing role of GABA from a trophic factor to that of a neurotransmitter. High levels of BDNF, NT-3 and MBP mRNA in the late gestational ages reveal that the human IC undergoes neuronal maturation, synaptogenesis and myelination by 29 WG. Therefore, it may be suggested that the morphological maturation of the human IC occurs between 22 and 29 WG and that this period appears to be critical in the shaping of adult-like physiological attributes.

Subplate Neurons Regulate Maturation of Cortical Inhibition and Outcome of Ocular Dominance Plasticity

Synaptic plasticity during critical periods of development requires intact inhibitory circuitry. We report that subplate neurons are needed both for maturation of inhibition and for the proper sign of ocular dominance (OD) plasticity. Removal of subplate neurons prevents the developmental upregulation of genes involved in mature, fast GABAergic transmission in cortical layer 4, including GABA receptor subunits and KCC2, and thus prevents the switch to a hyperpolarizing effect of GABA. To understand the implications of these changes, a realistic circuit model was formulated. Simulations predicted that without subplate neurons, monocular deprivation (MD) paradoxically favors LGN axons representing the deprived (less active) eye, exactly what was then observed experimentally. Simulations also account for published results showing that OD plasticity requires mature inhibition. Thus, subplate neurons regulate molecular machinery required to establish an adult balance of excitation and inhibition in layer 4, and thereby influence the outcome of OD plasticity.

The impact of chronic stress on the behaviors and the expression of brain-derived neurotrophic factor in the hippocampus of rats

目的 研究慢性不可预见性应激和孤养结合对大鼠外显行为及海马各亚区结构和BDNF表达的影响.方法应激组经过21d慢性应激后,观察所有大鼠行为学改变,用ABC法检测海马各亚区的BDNF表达.结果慢性应激后,应激组大鼠出现同抑郁症患者相似的行为改变;正常组大鼠BDNF在DG区(光密度为40.53±2.62,阳性面积比为2.013±0.074)和CA3区(光密度为39.09±3.19,阳性面积比为1.910±0.056)表达明显;海马各亚区BDNF同对照组相比明显下降(P<0.01).结论慢性不可预见性应激同孤养结合可建立较稳定的抑郁症模型;慢性应激可以使海马亚区BDNF表达下降;DG区和BDNF在海马可塑性上起到重要作用。

Retinoic acid‐induced neuronal differentiation regulates expression of mRNAs for neurotrophins and neurotrophin receptors in a human embryonal carcinoma cell line NTera2

The expression of mRNAs for neurotrophins and neurotrophin receptors was examined in NTera2/cl.D1 (NT2) human embryonal carcinoma cells at various stages of retinoic acid (RA)‐induced neuronal differentiation using reverse transcription‐polymerase chain reaction and southern blot analysis in order to investigate the biological role of neurotrophins in the human neuronal differentiation. The expression of high steady levels of BDNF, NT‐3, NT‐4, and low‐affinity NGF receptor mRNAs was observed in both untreated NT2 cells and NT2‐derived differentiated neurons induced by RA treatment. The lower levels of expression of NGF, trkA, trkB, and trkC mRNAs were identified in untreated NT2 cells and their expression was elevated markedly following 4 week treatment with RA. The increased expression of NGF, trkB, and trkC mRNAs were stable in NT2‐derived differentiated neurons, while the expression of trkA mRNA was reduced substantially in these cells. These results indicate that mRNAs for a battery of neurotrophins and their receptors are coexpressed in NT2 cells and their expression is regulated by RA‐induced neuronal differentiation.